DOP15 Results of a pragmatic multicentred randomised controlled trial investigating the use of personalised golimumab dosing in Ulcerative Colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis)

Abstract

Abstract Background Ulcerative Colitis (UC) is a chronic inflammatory bowel disease (IBD) often leading to impaired quality of life in affected patients. Current treatment modalities include anti-tumour necrosis factor (anti-TNF) monoclonal antibodies including infliximab, adalimumab and golimumab (GLM). RCT show higher trough drug levels (DL) following induction are associated with enhanced rates of remission in maintenance. GOAL-ARC is a pragmatic RCT to examine if dose optimisation of GLM following induction in response to suboptimal DL or persistently raised faecal calprotectin (FCP) improves rates of patient continuous clinical response (pCCR) and reduces maintenance disease activity in UC Methods A pragmatic randomised, multi-centre two-arm investigator initiated trial (NCT0268772) . Population – Patients with moderate to severe UC requiring TNF inhibitor therapy. Intervention - one arm receiving GLM treatment as per SMPC and one arm with dose optimisation of GLM based on FCP and DL from week 6 according to a dedicated algorithm. Eligible patients were randomised in a 1:1 ratio to 1 of 2 treatment groups. Study Duration - 46 weeks. Primary end-point pCCR = absence of flare defined as no increase in modified partial Mayo (MPM) score of 2 points from week 14-46 (requiring treatment intervention). Secondary endpoints included rate of clinical response to induction (week 14), defined as a drop of MPM of 2 points or decrease of ≥30% from baseline and level of FCP and rate of mucosal healing (Mayo endoscopic subscore of 0/1) at Wk 46 Results 107 patients were enrolled (target enrolment n=135, study enrolment terminated early due to recruitment problems during and following C19 pandemic). 97 patients (median age 42) were randomised, with one patient subsequently excluded due to ineligibility. Of 96 evaluable patients, 46 were randomised to SMPC treatment and 50 were randomised to the intervention. Baseline characteristic were comparable. 28/46 (61%) achieved wk 14 clinical response with SMPC and 19/46 (41%) met the primary endpoint (pCCR wk 14-46). In the intervention arm 28/50 (56%) achieved wk 14 clinical response and 24/50 (48%) met the primary endpoint (pCCR wk 14-46). The difference between groups in the rates of pCCR was 6.7% (95% CI:-0.15,0.29) in favour of the intervention and was not statistically significant. No safety signal associated with the intervention was observed. Conclusion In a pragmatic RCT no significant increase in the rate of pCCR was observed with personalised dosing of GLM for treatment of moderate to severe UC. A numerical trend towards reduced loss of response during maintenance (20% with SMPC versus 8% with intervention) is observed with personalised dosing of GLM suggesting this strategy may be beneficial in some patients